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PLoS ONE: Raltegrevir is a Potent Inhibitor of XMRV...

Discussion in 'XMRV Research and Replication Studies' started by parvofighter, Apr 1, 2010.

  1. parvofighter

    parvofighter Senior Member

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    Here's an update from the University of Utah on 45 compounds tested against XMRV:

    Powerful HIV drugs inhibit retrovirus linked to prostate cancer, chronic fatigue syndrome New study raises possibility of antiviral treatments for devastating illnesses

    From: http://www.eurekalert.org/pub_releases/2010-04/uouh-phd032910.php
    (SALT LAKE CITY)Certain drugs used to combat HIV also inhibit a retrovirus recently linked to prostate cancer and chronic fatigue syndrome (CFS), a new study from University of Utah and Emory University/Veterans Affair Medical Center (VA) researchers shows.

    The finding means that if the retrovirus XMRV (Xenotropic murine leukemia virus-related virus) is proved to cause prostate cancer or CFS, it's possible those two illnesses might one day be treatable with drugs aimed at HIV, the researchers write in a study published April 1, 2010, in PLoS One, an open-access journal published by the Public Library of Science (PLoS).

    "These results offer hope to infected persons, but we are still at the early stages of our understanding of the potential link between XMRV and these diseases," said Ila R. Singh, M.D., Ph.D., associate professor of pathology at the University of Utah School of Medicine. "Not all studies that have looked for XMRV have been able to detect it in prostate cancers or in samples from chronic fatigue syndrome. Even if XMRV is established to be the cause of prostate cancer or chronic fatigue syndrome, we will need to see the results of clinical trials before these drugs can be used in a clinical setting. We, along with other investigators, are working as hard as we possibly can to get to that point, but it is important to caution patients that we are not there yet."

    Singh, and Raymond F. Schinazi, Ph.D., D.Sc., professor of pediatrics and chemistry and an investigator with the Center for AIDS Research at the Emory University School of Medicine and the Atlanta VA, and colleagues tested 45 compounds used to treat HIV and other viral infections to see how effectively they worked against XMRV in cultured human breast cancer and prostate cancer cells. The most potent drug at inhibiting XMRV was raltegravir, made and marketed to treat HIV by Merck & Co., which inhibited XMRV replication in cultured cells at concentrations known to inhibit HIV in humans. Three other drugs, L-00870812, Zidovudine (ZDV or AZT), and tenofovir disoproxil fumarate (TDF), also effectively prevented virus replication. This study was not supported by Merck or any other pharmaceutical company that markets antiviral drugs.

    "Our study showed that these drugs inhibited XMRV at lower concentrations when two of them were used together, suggesting that possible highly potent 'cocktail' therapies might inhibit the virus from replicating and spreading," said Schinazi. "This combination of therapies might also have the added benefit of delaying or even preventing the virus from mutating into forms that are drug-resistant." Singh and Schinazi are currently investigating the development of viral resistance to raltegravir and other active drugs.

    XMRV, a retrovirus discovered in 2006 by researchers at the University of California, San Francisco, and at the Cleveland Clinic, is one of three retroviruses known to infect people. Other retroviruses that are closely related to XMRV are known to cause leukemia and sarcomas in animals. Last fall, Singh led a study that demonstrated the presence of XMRV in malignant human prostate cancer cells. That study, published in the Proceedings of the National Academy of Sciences, found XMRV in 27 percent of prostate cancers examined, with the virus more likely to be present in the most-aggressive tumors.

    More recently, scientists at the Whittemore Peterson Institute in Reno, Nev., identified XMRV in blood cells of patients with Chronic Fatigue Syndrome.
    ###
    Prostate cancer is the second most common cancer among males and strikes approximately 200,000 U.S. men annually. CFS, a debilitating condition that causes overwhelming fatigue and can be difficult to diagnose, affects an estimated 1 million to 4 million U.S. residents, according to the U.S. Centers for Disease Control and Prevention. If XMRV proves to be a causal factor in human diseases, these discoveries may allow for rational design of clinical trials.
  2. cfs since 1998

    cfs since 1998 *****

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    Wow, that is huge! Looks like I have a lot of updating to do. Thanks for posting!

    Here is the full text:
    http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009948
  3. parvofighter

    parvofighter Senior Member

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    Scientific American talking XMRV too

    FYI another version of the U of Utah update appeared in Scientific American Observations here: http://www.scientificamerican.com/blog/post.cfm?id=hiv-drugs-could-have-second-life-as-2010-04-01

    Apr 1, 2010 05:01 PM in Health & Medicine | Post a comment
    HIV drugs could have second life as treatment for retrovirus correlated with prostate cancer

    By Katherine Harmon
    Some medications already being used to treat HIV appear to inhibit a retrovirus that has been linked to prostate cancer and chronic fatigue syndrome, reports a new study published online April 1 in PLoS ONE.

    Like HIV (human immunodeficiency virus), XMRV (xenotropic murine leukemia virus-related virus) is a retrovirus that infects host cells with its RNA through reverse transcriptase enzymes, using protease enzymes to process proteins for viral assembly and integrase enzymes to help infect the host cell's DNA. Many of the drugs approved to treat HIV target one of these processes to slow or prevent host cells from becoming infected.

    After testing 28 approved drugs on XMRV cultures, researchers found that four of the medications (raltegravir, L-000870812, Zidovudine (AZT) and tenofovir disoproxil fumarate) were able to stop XMRV from replicating. Two of the drugs are reverse transcriptase inhibitors, and the others (including raltegravir, which worked the best) are integrase enzyme inhibitors.

    In addition to the similar success of the drugs' compounds, the researchers found that the use of the antiretrovirals might do well to follow HIV treatment protocol, in which multiple treatments are often used together. "These drugs inhibited XMRV at lower concentrations when two of them were used together, suggesting that highly potent 'cocktail' therapies might inhibit the virus from replicating and spreading," Raymond Schinazi, a professor of pediatrics and chemistry at Emory University's Center for AIDS Research, said in a prepared statement. "This combination of therapies might also have the added benefit of delaying or even preventing the virus from mutating into forms that are drug-resistant."

    XMRV is one of only a few retroviruses known in humans and was found in 2006. Since then, some studies have found a correlation between it and some forms of prostate cancer (which is the second most common cancer among men) as well as chronic fatigue syndrome (estimated to affect four to 10 people per thousand). Other studies have had mixed results, so the implications of the results hinge largely on future findings about this retrovirus's role in human disease. "It is not yet clear if any illnesses are directly caused by XMRV," the researchers wrote in their study. But "our data indicates that XMRV infections might be prevented or treated with specific antiviral agents."

    And if the retrovirus does prove to play a role in causing illnesses, the findings could help in designing clinical trials to test the treatments in vivo.

    In the meantime, Ila Singh, an associate professor of pathology at the University of Utah School of Medicine and lead author on the new study, concluded in a prepared statement that, "These results offer hope to infected persons."

  4. parvofighter

    parvofighter Senior Member

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    And Healthfinder.gov

    XMRV making a splash at Healthfinder.gov too!:Retro smile:

    From: http://www.healthfinder.gov/news/newsstory.aspx?docID=637521HIV Drugs Might Combat Two Other Diseases

    Prostate cancer, chronic fatique are new research targets.

    THURSDAY, April 1 (HealthDay News) -- Four anti-HIV drugs inhibit a retrovirus recently linked to prostate cancer and chronic fatigue syndrome (CFS), say U.S. researchers.
    If further investigation proves that the retrovirus xenotropic murine leukemia virus-related virus (XMRV) causes prostate cancer or CFS, these HIV drugs may be an effective treatment for the two conditions.

    In this study, researchers from the University of Utah and Emory University/Veterans Affair Medical Center tested how effectively 45 compounds used to treat HIV and other viral infections worked against XMRV. Raltegravir was the most effective, and three other drugs -- L-00870812, zidovudine (ZDV or AZT), and tenofovir disoproxil fumarate (TDF) -- also prevented XMRV replication.
  5. omerbasket

    omerbasket Senior Member

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    shouldn't this new study be in a seperate thread? I think it deserves it...
    Anyway, there is a nice graph on the plosone website, I think it's regearding the effectivitey of increasing dosages of those 4 drugs relating to their inhibition of XMRV and their effect of regular human cells. I didn't really understand the graph completely and I would be glad if someone here can clarify it.

    By the way, what is L-000870812? Is there a way to know about it's side effects?
  6. parvofighter

    parvofighter Senior Member

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  7. Frickly

    Frickly Senior Member

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    "HIV drugs could have second life as treatment for retrovirus correlated with prostate cancer"
    By Katherine Harmon



    "Some medications already being used to treat HIV appear to inhibit a retrovirus that has been linked to prostate cancer and chronic fatigue syndrome, reports a new study published online April 1 in PLoS ONE.

    Like HIV (human immunodeficiency virus), XMRV (xenotropic murine leukemia virus-related virus) is a retrovirus that infects host cells with its RNA through reverse transcriptase enzymes, using protease enzymes to process proteins for viral assembly and integrase enzymes to help infect the host cell's DNA. Many of the drugs approved to treat HIV target one of these processes to slow or prevent host cells from becoming infected.

    After testing 28 approved drugs on XMRV cultures, researchers found that four of the medications (raltegravir, L-000870812, Zidovudine (AZT) and tenofovir disoproxil fumarate) were able to stop XMRV from replicating. Two of the drugs are reverse transcriptase inhibitors, and the others (including raltegravir, which worked the best) are integrase enzyme inhibitors.

    In addition to the similar success of the drugs' compounds, the researchers found that the use of the antiretrovirals might do well to follow HIV treatment protocol, in which multiple treatments are often used together. "These drugs inhibited XMRV at lower concentrations when two of them were used together, suggesting that highly potent 'cocktail' therapies might inhibit the virus from replicating and spreading," Raymond Schinazi, a professor of pediatrics and chemistry at Emory University's Center for AIDS Research, said in a prepared statement. "This combination of therapies might also have the added benefit of delaying or even preventing the virus from mutating into forms that are drug-resistant."

    XMRV is one of only a few retroviruses known in humans and was found in 2006. Since then, some studies have found a correlation between it and some forms of prostate cancer (which is the second most common cancer among men) as well as chronic fatigue syndrome (estimated to affect four to 10 people per thousand). Other studies have had mixed results, so the implications of the results hinge largely on future findings about this retrovirus's role in human disease. "It is not yet clear if any illnesses are directly caused by XMRV," the researchers wrote in their study. But "our data indicates that XMRV infections might be prevented or treated with specific antiviral agents."

    And if the retrovirus does prove to play a role in causing illnesses, the findings could help in designing clinical trials to test the treatments in vivo.

    In the meantime, Ila Singh, an associate professor of pathology at the University of Utah School of Medicine and lead author on the new study, concluded in a prepared statement that, "These results offer hope to infected persons."
  8. VillageLife

    VillageLife Senior Member

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    Scientific American - HIV Drugs for XMRV (April 1st)

    http://www.scientificamerican.com/blog/post.cfm?id=hiv-drugs-could-have-second-life-as-2010-04-01

    In Scentific American:

    HIV drugs could have second life as treatment for retrovirus correlated with prostate cancer
    By Katherine Harmon

    Some medications already being used to treat HIV appear to inhibit a retrovirus that has been linked to prostate cancer and chronic fatigue syndrome, reports a new study published online April 1 in PLoS ONE.

    Like HIV (human immunodeficiency virus), XMRV (xenotropic murine leukemia virus-related virus) is a retrovirus that infects host cells with its RNA through reverse transcriptase enzymes, using protease enzymes to process proteins for viral assembly and integrase enzymes to help infect the host cell's DNA. Many of the drugs approved to treat HIV target one of these processes to slow or prevent host cells from becoming infected.

    After testing 28 approved drugs on XMRV cultures, researchers found that four of the medications (raltegravir, L-000870812, Zidovudine (AZT) and tenofovir disoproxil fumarate) were able to stop XMRV from replicating. Two of the drugs are reverse transcriptase inhibitors, and the others (including raltegravir, which worked the best) are integrase enzyme inhibitors.

    In addition to the similar success of the drugs' compounds, the researchers found that the use of the antiretrovirals might do well to follow HIV treatment protocol, in which multiple treatments are often used together. "These drugs inhibited XMRV at lower concentrations when two of them were used together, suggesting that highly potent 'cocktail' therapies might inhibit the virus from replicating and spreading," Raymond Schinazi, a professor of pediatrics and chemistry at Emory University's Center for AIDS Research, said in a prepared statement. "This combination of therapies might also have the added benefit of delaying or even preventing the virus from mutating into forms that are drug-resistant."

    XMRV is one of only a few retroviruses known in humans and was found in 2006. Since then, some studies have found a correlation between it and some forms of prostate cancer (which is the second most common cancer among men) as well as chronic fatigue syndrome (estimated to affect four to 10 people per thousand). Other studies have had mixed results, so the implications of the results hinge largely on future findings about this retrovirus's role in human disease. "It is not yet clear if any illnesses are directly caused by XMRV," the researchers wrote in their study. But "our data indicates that XMRV infections might be prevented or treated with specific antiviral agents."

    And if the retrovirus does prove to play a role in causing illnesses, the findings could help in designing clinical trials to test the treatments in vivo.

    In the meantime, Ila Singh, an associate professor of pathology at the University of Utah School of Medicine and lead author on the new study, concluded in a prepared statement that, "These results offer hope to infected persons."






    *
  9. Adam

    Adam *****

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    Great find. More 'positive news'. The Utah people look to be very serious about XMRV. I imagine in the coming weeks we will get more news of this kind. You never know we might even get blase about it?

    I saw my infectious diseases consultant today. He had at least heard of the WPI study and the British one of course. I said to him 'I wonder if the NHS will treat CFS patients with anti-virals if and when the cause is established. He said 'the NHS is good at treating stuff that can be treated'. Fair enough comment I thought.

    I also dropped in the fact that Glaxo Smith and Kline had thrown their hat in the ring. He appeared impressed that they were involved at his early stage. Although he did throw in that US drug companies marketed their products like Coca-Cola!
  10. Frickly

    Frickly Senior Member

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    PLoS ONE Study Published Today

    "Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome"

    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009948

    "Xenotropic murine leukemia-related retrovirus (XMRV) is a recently discovered retrovirus that has been linked to human prostate cancer and chronic fatigue syndrome (CFS). Both diseases affect a large fraction of the world population, with prostate cancer affecting one in six men, and CFS affecting an estimated 0.4 to 1% of the population."

    "Forty-five compounds, including twenty-eight drugs approved for use in humans, were evaluated against XMRV replication in vitro. We found that the retroviral integrase inhibitor, raltegravir, was potent and selective against XMRV at submicromolar concentrations, in MCF-7 and LNCaP cells, a breast cancer and prostate cancer cell line, respectively. Another integrase inhibitor, L-000870812, and two nucleoside reverse transcriptase inhibitors, zidovudine (ZDV), and tenofovir disoproxil fumarate (TDF) also inhibited XMRV replication. When combined, these drugs displayed mostly synergistic effects against this virus, suggesting that combination therapy may delay or prevent the selection of resistant viruses."

    "If XMRV proves to be a causal factor in prostate cancer or CFS, these discoveries may allow for rational design of clinical trials."
  11. shrewsbury

    shrewsbury member

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    Wow Frickly - great find! But, if I can say this without being too forthright or too rude, you do have to work on your titles. Plos one brought negative memories. We need something like:'New XMRV findings' or better to wet people's appetites.

    This is an Ila Singh and colleagues study. And look at the other people involved: Center for AIDS Research at Emory. Funded in part by NIH and by the Department of Veterans Affairs (RFS)! And getting ready for "rational design of clinical trials" of effective drugs


  12. justinreilly

    justinreilly Stop the IoM & P2P! Adopt CCC!

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    Great! Nice to see promise in a few anti-retrovirals with a synergistic effect. And the discussion and abstract give more accurate info on ME/CFIDS than the vast majority of articles.

    I will be nitpicky here. A quote from the study:
    It's nice that he at least qualifies his statement that GET is effective. But there are still problems with this statement.

    He says that GET appears to exert a positive treatment effect by improving coping skills rather than reducing symptoms. He sites a 2000 article by Chalder and Wessely. One problem is the Wessely article doesn't support the statement. (It, of course, just says that GET is the greatest thing since sliced bread for reducing "CFS" symptoms).

    A second problem is that there is no credible evidence (of which I am aware, pls correct me if mistaken) showing that GET helps Canadian or Fukuda described ME patients. Studies using the "Oxford" definition are patently invalid as this definition merely describes idiopathic chronic fatigue, not the discrete disease ME/CFIDS.

    The third problem is that there is good evidence that GET causes substantial iatrogenic morbidity in a large percentage of ME patients.

    The fourth problem is that it does not seem even theoretically possible that GET could improve coping skills (well administered CBT could theoretically improve coping skills and this is probably just a sloppy conflation of CBT and GET on the author's part).
  13. fred

    fred The game is afoot

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  14. shrewsbury

    shrewsbury member

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    woohoo - Scientific American publishes an article onthe Ila Singh et al research into HIV drugs that may work for XMRV (with full prostate cancer and ME/CFS references) on the same day that the research is published!
  15. Hope123

    Hope123 Senior Member

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  16. starryeyes

    starryeyes Senior Member

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    "Conclusions

    If XMRV proves to be a causal factor in prostate cancer or CFS, these discoveries may allow for rational design of clinical trials."

    This is very exciting!
  17. Andrew

    Andrew Senior Member

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  18. Otis

    Otis SeƱor Mumbler

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    So true. But, if we can gain legitimacy, awareness AND treatment from those marketing $s, I'll take it!

    Otis
  19. Frickly

    Frickly Senior Member

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    Uggg! I know! I have 2 four year olds, 2 eight year olds, two eleven year olds and 3 dogs in my house right now. All these kids need to go play at someone at someone elses house! :)

    Please feel free to change the title.......

  20. usedtobeperkytina

    usedtobeperkytina Senior Member

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    ok, I have some questions.

    Is this the April surprise or are we to expect more news in April? Cort, you seem to be piped into the rumor mill. What can you find out?

    Secondly, are any of these drugs made by GSK? That might explain some things.

    I noticed one is made by Merck. So expect an announcement from them at some point.

    And, does the comment about combination help in not making resistant virus mean that if this works, we may not have to change drugs often as HIV patients do?

    Also, what happened to the estimation of a test being available within a month of the Jan. 22 speech. (It was on Jan. 22 that she said that, right?)

    Isn't it interesting that these tests of drug efficacy is coming out before a true replication study confirms it is in CFS patients? Either these others really believe the WPI or are just running on the assumption. I know it is in prostate cancer too. But that is not what is behind these studies. Maybe just proof it infects is enough to cause these studies. But notice the comment that this may bring hope to CFs patients. Well, only if CFS patients have XMRV. She must know it or see strong evidence to believe it.

    Tina

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